Research Square (Research Square),
Journal Year:
2021,
Volume and Issue:
unknown
Published: Nov. 12, 2021
Abstract
Background:
The
potential
functions
of
circular
RNAs
(circRNAs)
and
micro
(miRNAs)
in
osteosarcoma
(OS)
have
not
been
fully
elucidated.
Especially,
the
behavior
mechanism
immune
responses
OS
development
progression
demonstrated.
It
was
reported
that
circRNAs
miRNAs
can
serve
as
biomarkers
for
diagnosis,
prognosis,
therapy
many
cancers.
This
study
aimed
to
identify
novel
key
serum
diagnose
predict
metastasis
based
on
analysis
cell
infiltration
characteristics.
Methods:
differentially-expressed
(DEcircRNAs),
(DEmiRNAs),and
mRNAs
(DEmRNAs)
human
were
investigated
microarray
data
downloaded
from
Gene
Expression
Omnibus
(GEO)
datasets.
Then,
we
analyzed
characteristics
pattern
tumor-infiltrating
cells
OS.
On
this
basis,
identified
statistically-significant
transcription
factors
performed
pathway
enrichment
analysis.
Subsequently,
constructed
protein-protein
interaction
(PPI)
competitive
endogenous
RNA
(ceRNA)
networks.
Moreover,
biological
characteristic
targets
ceRNA
networks
proposed.
Finally,
expression
diagnostic
capability
these
network
confirmed
by
RT-qPCR
patients’
serum.
Results:
Seven
166
(DEmiRNAs)
175
total.
highest
level
patients
M0
macrophages,
M2
macrophages
CD8+
T
cells.
Further,
showed
largest
negative
correlation
coefficients.
These
significant
revealed
principal
component
found
185
which
main
molecules
show
immunotherapy
Hsa-circ-0010220,
hsa-miR-326,
hsa-miR-338-3p,
FAM98A
associated
with
could
distinguish
metastasis.
Most
importantly,
a
model
consisting
four
promising
(hsa-circ-0010220,
FAM98A)
highlighted
0.928
AUC
value.
Conclusions:
In
summary,
potenial
found,
proposed
firstly.
results
provided
new
perspective
Frontiers in Molecular Biosciences,
Journal Year:
2021,
Volume and Issue:
8
Published: May 24, 2021
Lung
cancer
is
a
serious
malignancy,
and
lung
adenocarcinoma
(LUAD)
the
most
common
pathological
subtype.
Immune-related
factors
play
an
important
role
in
lymph
node
metastasis.
In
this
study,
we
obtained
gene
expression
profile
data
for
LUAD
normal
tissues
from
TCGA
database
analyzed
their
immune-related
genes
(IRGs),
observed
that
459
IRGs
were
differentially
expressed.
Further
analysis
of
correlation
between
expressed
metastasis
revealed
18
metastasis-associated
IRGs.
addition,
mutations
status,
function
pathway
enrichment
these
IRGs,
regulatory
networks
established
through
TF
genes.
We
then
identified
eight
(IKBKB,
LTBR,
MIF,
PPARD,
PPIA,
PSME3,
S100A6,
SEMA4B)
as
best
predictors
by
LASSO
Logistic
used
to
construct
model
predict
patients
with
(AUC
0.75;
95%
CI:
0.7064–0.7978),
survival
showed
risk
score
independently
affected
patient
survival.
validated
predictive
effect
scores
on
using
GEO
validation
cohort
results
good
agreement.
was
highly
correlated
infiltration
immune
cells
(mast
activated,
macrophages
M2,
M0
B
naïve),
stromal
scores,
checkpoint
(LTBR,
CD40LG,
EDA2R,
TNFRSF19).
key
associated
constructed
reliable
model,
which
may
provide
valuable
biomarkers
further
reveal
mechanism
its
occurrence.
Journal of Cancer Research and Clinical Oncology,
Journal Year:
2024,
Volume and Issue:
150(2)
Published: Jan. 29, 2024
Abstract
Osteosarcoma
(OS)
is
the
most
common
malignancy
in
children
and
adolescents
has
a
high
probability
of
recurrence
metastasis.
A
growing
number
studies
have
shown
that
neutrophil
extracellular
traps
(NETs)
are
strongly
associated
with
cancer
metastasis,
but
osteosarcoma,
genes
NETs
promote
osteosarcoma
metastasis
remain
to
be
explored.
We
systematically
investigated
gene
expression
patterns
OS
samples
from
GEO
database.
molecular
typing
was
evaluated
based
on
profiles,
association
between
subtypes
immune
microenvironment
metastatic
features
were
Ultimately,
we
constructed
signature
model
column
line
graph
prediction
screened
possible
potential
drugs
for
osteosarcoma.
established
two
different
NETs,
which
showed
significant
differences
status,
time,
tumor
microenvironment,
biological
effects.
also
NETs-related
signature(NRGMS)
assess
pattern
patients
predict
patients.
TOMM40
FH
Overall,
this
study
constructs
predictive
genes,
expected
provide
new
insights
into
Journal of Biomedical Science,
Journal Year:
2024,
Volume and Issue:
31(1)
Published: June 5, 2024
Abstract
Osteosarcoma
(OS)
is
the
most
prevalent
and
fatal
type
of
bone
tumor.
It
characterized
by
great
heterogeneity
genomic
aberrations,
mutated
genes,
cell
types
contribution,
making
therapy
patients
management
particularly
challenging.
A
unifying
picture
molecular
mechanisms
underlying
disease
could
help
to
transform
those
challenges
into
opportunities.
This
review
deeply
explores
occurrence
in
OS
large-scale
RNA
regulatory
networks,
denominated
“competing
endogenous
network”
(ceRNET),
wherein
different
biotypes,
such
as
long
non-coding
RNAs,
circular
RNAs
mRNAs
can
functionally
interact
each
other
competitively
binding
shared
microRNAs.
Here,
we
discuss
how
unbalancing
any
network
component
derail
entire
circuit,
driving
onset
progression
impacting
on
proliferation,
migration,
invasion,
tumor
growth
metastasis,
even
chemotherapeutic
resistance,
distilled
from
many
studies.
Intriguingly,
aberrant
expression
networks
components
cells
be
triggered
also
surroundings,
through
cytokines
vesicles,
with
their
bioactive
cargo
proteins
highlighting
relevance
microenvironment.
comprehensive
pave
way
for
development
innovative
RNA-targeted
RNA-based
therapies
new
diagnostic
tools,
perspective
precision
oncology.
International Journal of Biological Sciences,
Journal Year:
2021,
Volume and Issue:
17(7), P. 1629 - 1643
Published: Jan. 1, 2021
Long
non-coding
RNA
(lncRNA)
small
nucleolar
host
gene
12
(SNHG12)
plays
important
roles
in
the
pathogenesis
and
progression
of
cancers.However,
role
SNHG12
metastasis
gastric
cancer
(GC)
has
not
yet
been
thoroughly
investigated.In
present
study,
we
demonstrated
that
was
upregulated
GC
tissues
cell
lines.In
addition,
expression
level
samples
significantly
related
to
tumor
invasion
depth,
TNM
stage
lymph
node
associated
with
disease-free
survival
(DFS)
overall
(OS)
patients.In
vivo
vitro
assays
indicated
promotes
epithelial-mesenchymal
transition
(EMT).Bioinformatics
mechanistic
analyses
revealed
can
directly
target
miR-218-5p
regulate
YWHAZ
mRNA,
forming
an
SNHG12/miR-218-5p/YWHAZ
axis
decreasing
ubiquitination
β-catenin.In
stabilizes
CTNNB1
mRNA
by
binding
HuR,
thus
activating
β-catenin
signaling
pathway.Further
analysis
also
transcription
factor
YY1
negatively
modulates
transcription.In
conclusion,
is
a
potential
prognostic
marker
therapeutic
for
GC.Negatively
modulated
YY1,
EMT
regulating
miR-218-5p/YWHAZ
stabilizing
via
activation
pathway.
Frontiers in Immunology,
Journal Year:
2022,
Volume and Issue:
13
Published: Dec. 23, 2022
Background
Glycolysis
and
cholesterol
synthesis
are
crucial
in
cancer
metabolic
reprogramming.
The
aim
of
this
study
was
to
identify
a
glycolysis
synthesis-related
genes
(GCSRGs)
signature
for
effective
prognostic
assessments
osteosarcoma
patients.
Methods
Gene
expression
data
clinical
information
were
obtained
from
GSE21257
TARGET-OS
datasets.
Consistent
clustering
method
used
the
GCSRGs-related
subtypes.
Univariate
Cox
regression
LASSO
analyses
construct
GCSRGs
signature.
ssGSEA
analyze
differences
immune
cells
infiltration.
pRRophetic
R
package
utilized
assess
drug
sensitivity
different
groups.
Western
blotting,
cell
viability
assay,
scratch
assay
Transwell
perform
cytological
validation.
Results
Through
bioinformatics
analysis,
patients
diagnosed
with
classified
into
one
4
subtypes
(quiescent,
glycolysis,
cholesterol,
mixed
subtypes),
which
differed
significantly
terms
prognosis
tumor
microenvironment.
Weighted
gene
co-expression
network
analysis
revealed
that
modules
strongly
correlated
midnight
blue
yellow
modules,
respectively.
Both
univariate
conducted
on
screened
module
5
(RPS28,
MCAM,
EN1,
TRAM2,
VEGFA)
constituting
an
predictor,
independent
characteristics,
as
verified
further
via
Kaplan-Meier
ROC
curve
multivariate
analysis.
Additionally,
had
strong
correlation
sensitivity,
checkpoints
In
experiments,
we
selected
TRAM2
representative
validate
validity
signature,
found
promoted
progression
cells.
Finally,
at
pan-cancer
level,
been
overall
survival,
free
disease
specific
mutational
burden,
microsatellite
instability,
Conclusion
Therefore,
constructed
efficiently
predicted
patient
guided
therapy.
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(23), P. 14978 - 14978
Published: Nov. 29, 2022
There
are
currently
no
effective
biomarkers
for
prognosis
and
optimal
treatment
selection
to
improve
non-small
cell
lung
cancer
(NSCLC)
survival
outcomes.
This
study
further
validated
a
seven-gene
panel
diagnosis
of
NSCLC
using
RNA
sequencing
proteomic
profiles
patient
tumors.
Within
the
panel,
ZNF71
expression
combined
with
dendritic
activities
defined
subgroups
(n
=
966)
distinct
outcomes
(p
0.04,
Kaplan-Meier
analysis).
was
significantly
associated
natural
killer
cells
0.014)
T
0.003)
in
tumors
1016)
Chi-squared
tests.
Overexpression
resulted
decreased
multiple
components
intracellular
intrinsic
innate
immune
systems,
including
dsRNA
dsDNA
sensors.
Multi-omics
networks
systems
were
computed
as
relevant
tumorigenesis,
proliferation,
clinical
information
in-vitro
CRISPR-Cas9/RNAi
screening
data.
From
these
networks,
pan-sensitive
pan-resistant
genes
21
NCCN-recommended
drugs
treating
selected.
Based
on
gene
associations
CRISPR-Cas9,
RNAi,
drug
data,
MEK1/2
inhibitors
PD-198306
U-0126,
VEGFR
inhibitor
ZM-306416,
IGF-1R
PQ-401
discovered
potential
targeted
therapy
that
may
also
induce
an
response
NSCLC.
International Journal of Applied Pharmaceutics,
Journal Year:
2024,
Volume and Issue:
unknown, P. 280 - 287
Published: Jan. 7, 2024
Objective:
To
demonstrate
the
efficacy
and
benefits
of
aporphine
alkaloids
from
Nelumbo
nucifera
Gaertn.
as
anti-breast
cancer
agents.
Methods:
In
this
study,
a
combination
network
pharmacology
molecular
docking
was
used
to
investigate
pharmacological
actions
underlying
mechanisms
action
nuciferine,
nor-nuciferine,
roemerine
against
breast
cancer.
Results:
Fifty-five
potential
targets
compounds
were
identified.
The
Epidermal
Growth
Factor
Receptor
(EGFR),
Mitogen-Activated
Protein
Kinase
8
(MAPK8),
Janus
2
(JAK2),
Inhibitor
Nuclear
Kappa
B
Subunit
Beta
(IKBKB),
C
Epsilon
(PRKCE)
identified
top
five
Molecular
demonstrated
that
these
could
bind
spontaneously
screened
4
targeted
proteins.
Conclusion:
present
study
demonstrates
have
effects
via
multi-target
multi-pathway
manner.
Engineering,
Journal Year:
2022,
Volume and Issue:
21, P. 188 - 194
Published: Jan. 4, 2022
Osteosarcoma
(OS)
is
a
malignant
mesenchymal
tissue
tumor
known
to
occur
in
children
and
adolescents,
pulmonary
metastasis
often
leads
death
these
patients.
The
mechanism
underlying
OS
progression
remains
unclear.
Therefore,
identifying
new
therapeutic
targets
treatment
modalities
for
urgently
needed.
Abnormally
expressed
non-coding
circular
RNAs
(circRNAs)
are
crucial
the
occurrence
development
of
OS.
purpose
this
study
was
explore
expression
role
novel
circRNA
circ_000203
elucidate
mechanism.
demonstrated
highly
cell
lines
tissues,
knockdown
significantly
inhibited
vitro
vivo.
Furthermore,
we
found
that
sponge
miR-26b-5p,
an
upstream
regulator
bone
morphogenetic
protein
receptor
2
(BMPR2).
Thus,
overexpression
BMPR2
could
reduce
inhibitory
effect
on
progression.
This
indicates
suppresses
through
microRNA
(miRNA)-mediated
downregulation.
Our
findings
provide
important
insights
understanding
Cancer Science,
Journal Year:
2021,
Volume and Issue:
113(1), P. 120 - 131
Published: Sept. 30, 2021
Osteosarcoma
(OS)
is
a
primary
and
highly
malignant
mesenchymal
tissue
tumor.
The
specific
pathological
mechanism
underlying
disease
initiation
or
progression
remains
unclear.
Circular
RNAs
(circRNAs)
are
type
of
covalently
circular
RNA
with
head-to-tail
junction
site.
In
this
study,
we
aimed
to
investigate
the
sponging
between
circRNAs
microRNAs
(miRNAs)
in
OS.
Based
on
inhibited
effect
miR-16-5p
reported
OS,
circUSP34
was
analyzed
as
sponge
via
Starbase.
We
found
that
promoted
proliferation,
migration,
invasion
OS
vitro
vivo.
increased
but
decreased
by
qRT-PCR.
Function
assays
showed
malignancy
cells,
including
invasion,
after
knocking
out
circUSP34.
Western
blotting
results
expression
level
vimentin
Ki-67
decreased.
Similarly,
mimic
compromised
cells.
FISH
assay
indicated
were
colocalized
cytoplasm.
verified
dual-luciferase
reporter
assay,
immunoprecipitation
(RIP),
pull
down
assays.
Interestingly,
inhibitor
partly
reversed
inhibitory
sh-circUSP34
Further,
mice
tumors
for
IHC
vimentin,
N-cadherin,
protein
decreased,
E-cadherin
increased.
Collectively,
malignancy,
miR-16-5p.
It
can
serve
potential
therapeutic
target
biomarker.
Genome biology,
Journal Year:
2021,
Volume and Issue:
22(1)
Published: Oct. 7, 2021
The
diversity
of
genomic
alterations
in
cancer
poses
challenges
to
fully
understanding
the
etiologies
disease.
Recent
interest
infrequent
mutations,
genes
that
reside
"long
tail"
mutational
distribution,
uncovered
new
with
significant
implications
development.
study
cancer-relevant
often
requires
integrative
approaches
pooling
together
multiple
types
biological
data.
Network
propagation
methods
demonstrate
high
efficacy
achieving
this
integration.
Yet,
majority
these
focus
their
assessment
on
detecting
known
or
identifying
altered
subnetworks.
In
paper,
we
introduce
a
network
approach
entirely
focuses
prioritizing
long
tail
potential
functional
impact